Dengue virus (DENV) is an important mosquito-borne virus represented by four serotypes: DENV1–DENV4. In Cell, Sasisekharan and colleagues use a structure-guided approach to generate antibodies broadly cross-reactive to all four DENV serotypes. Humoral responses generally result in good protective memory to a given serotype but usually poor heterologous protection. Despite this, the humoral response can include broadly reactive neutralizing antibodies, but they are usually only a minor component of the repertoire. On the basis of the epitope-paratope binding of a previously described antibody to DENV, the authors redesign an antibody with enhanced affinity for and neturalizing effect on all four serotypes. This antibody, Ab513, is also protective against all four serotypes in multiple mouse models of DENV infection. This study demonstrates how rational design of antibodies could lead to effective passive immunotherapy against DENV and potentially other pathogenic viruses that otherwise elicit only weakly neutralizing responses.

Cell (30 July 2015) doi:10.1016/j.cell.2015.06.057